A key component of this program project is bringing appropriate technical expertise to the Projects. This includes both new advances in human neuroimaging (an Imaging Core) and provision of key animal imaging techniques (an Animal Core). This scientific core will therefore have two parts. The Imaging Core will focus on key technical targets that are critical to improve the quality of data required for Project 3 (imaging of migraine effects in humans), and lay the groundwork for eventual human translation of work proposed for Project 1 (cortical spreading depression [CSD] treatment) or Project 2 (CSD and linkage to neuronal hyperstimulation) Specifically, the Imaging Core will provide two broad functions. First, the Core will provide technical support in four specific areas to directly assist in accomplishing the specific aims of Project 1 and Project 2 and ensure that the technical solutions are in place to accomplish the proposed aims. This will be accomplished both through the explicit goals of the Focus Areas as well as using the Imaging Core as a vehicle to assemble technical expertise to flexibly advise and assist the project leaders and their teams. Second, the Core will further develop additional technologies, in these same four specific focus areas, that will be helpful in elucidating the pathophysiology and treatment mechanisms of migraine: that is, to keep advancing the state of the art of neuroimaging in migraine. Part 2 of the Scientific Core will support Project 1 and 2 and perform imaging studies in rodents. Specifically, immunohistochemical studies will examine the phosphorylation state of the protein kinase Erk (Project 2) and examine the distribution of proteins encoded by mRNA with altered expression following chronic antimigraine drug treatment (Project 1). In addition, in situ hybridization studies will confirm the results of gene array studies (Project 1), while in vitro receptor autoradiography will examine the density and affinity of various glutamate receptor subtypes that may be involved in the generation/propagation ofCSD.